title: Exploration of new scaffolds as potential MAO-A inhibitors using pharmacophore and 3D-QSAR based in silico screening.
abstract: Monoamine oxidase-A (MAO-A) inhibitors are of particular importance in the treatment of depressive disorders. Herein described is pharmacophore generation and atom-based 3D-QSAR analysis of previously reported pyrrole based MAO-A inhibitors in order to get insight into their structural requirements responsible for high affinity. The best pharmacophore model generated consisted of four features DHHR: a hydrogen bond donor (D), two hydrophobic groups (H) and an aromatic ring (R). Based on model generated, a statistically valid 3D-QSAR with good predictability was developed. Derived pharmacophore was used as a query to search Zinc 'clean drug-like' database. Hits retrieved were passed progressively through filters like fitness score, predicted activity and docking scores. The survived hits present new scaffolds with a potential for MAO-A inhibition.
authors.affiliation: Department of Pharmaceutical Chemistry, Bharati Vidyapeeth Deemed University, Poona College of Pharmacy, Pune 411 038, Maharashtra, India.
authors.forename: Suhas M
authors.initials: SM
authors.lastname: Shelke
authors.forename: Sharad H
authors.initials: SH
authors.lastname: Bhosale
authors.forename: Radha Charan
authors.initials: RC
authors.lastname: Dash
authors.forename: Mugdha R
authors.initials: MR
authors.lastname: Suryawanshi
authors.forename: Kakasaheb R
authors.initials: KR
authors.lastname: Mahadik
mesh_terms: D001665:Binding Sites; D020134:Catalytic Domain; D003198:Computer Simulation; D016208:Databases, Factual; D008995:Monoamine Oxidase / Q000737:chemistry* / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship
chemical_list: D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase